The objective of the proposed research is to map the opiate mu receptor. Two approaches will be taken: one is X-ray structure determination of drug molecules that are active at the receptor site, and the second is receptor site modeling by computer simulation. In the first approach, X-ray crystallographic methods will be used to determine the geometry, electron density distribution (EDD) and molecular electrostatic potential (MEP) of the drug molecules, which include naloxone, morphine, methadone and their derivatives. Using the concept of lock-and-key mechanism of ligand-receptor binding, the active site will be modeled based on a structure complementary to these ligand molecules. Considerable data already exist from the investigator's previous and ongoing studies on the ligand molecules. A trial program on the receptor modeling has been written to fit surfaces to the geometry of these molecules, and to improve and develop the computer program for the modeling of the receptor site.